The central hypothesis of Project 2, Energy Balance and Metabolism, is that dietary restriction (DR) increases longevity through changes in energy and substrate metabolism. DR is the only known environmental intervention that consistently increases life span. Because there is a striking relationship between the level of caloric restriction and the magnitude of life extension in rodents, the study of energy metabolism is a fundamental pursuit for probing the actions of DR in primates. Accordingly, we propose to continue our pursuits in this area and have identified the following specific aims. These are to characterize the independent and interactive effects of age and DR on: 1. Body composition to the finest level resolvable; 2. Multiple facets of substrate metabolism, including energy expenditure and glucose homeostasis. effects of body composition on these outcomes will also be evaluated; 3. The bioactivity of adipose tissue. To date, we have documented significant reductions in chronic disease risk factors including decreased obesity, maintenance of fat-free mass, improved insulin sensitivity, and absence of type 2 diabetes. During the coming five years, we will utilize the PPG animals to test the general hypotheses that DR will increase health span and, eventually life span, as displayed by reduced fat mass and metabolic rate, and maintenance of fat-free mass, skeletal muscle mass, and insulin sensitivity. A linking hypothesis is that the effects of DR will be mediated through changes in adipose tissue signals.